BEGONIA: Dato-DXd Plus Durvalumab Achieves ‘Robust Response’ In Advanced TNBC

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: The BEGONIA trial investigators have reported positive initial findings for the first-line combination of datopotamab deruxtecan (Dato-DXd) and durvalumab in patients with locally advanced or metastatic triple-negative breast cancer (TNBC) who were unselected by PD-L1 expression. 

Peter Schmid, from Barts Cancer Institute in London, UK, presented the phase Ib/II platform trial results at the ESMO Breast Cancer 2022 in Berlin, Germany, for 29 patients given the antibody–drug conjugate (ADC) Dato-DXd 6 mg/kg and the PD-L1 inhibitor durvalumab 1120 mg at 3-week intervals, with treatment ongoing in 83% of the group at data cutoff. 

After a median of 3.9 months, a “robust response rate” of 74% was achieved among the 27 evaluable patients, he said, comprising a complete response in 7% and a partial response in 67%. 

Responses occurred after a median of 1.4 months and all patients had ongoing responses at time of data cutoff, with the median duration of response yet unreached. 

While most patients (72.4%) had low PD-L1 expression of less than 5%, 17.2% had high levels and 10.3% unknown; Peter Schmid emphasized that “responses were seen regardless of PD-L1 expression.” 

The presenter said that patients had not previously been treated for stage IV disease; approximately one-third of patients had de novo metastatic disease, while around two-thirds had received a range of treatments for early-stage TNBC, such as cytotoxic chemotherapy (66%), radiotherapy (59%), anthracyclines (55%) and taxanes (48% with a minimum 12-month interval prior to enrolment).  

Of note, 21% of patients had previously received hormone therapy and 7% targeted therapy for primary breast cancer and subsequently developed TNBC over time, Schmid said. 

There were no dose-limiting toxicities and the combination had a “manageable safety profile”, the investigator observed, with grade 3–4 treatment-related adverse events in 28% of patients. Most patients were treated at the planned Dato-DXd dose, with 14% requiring a dose reduction and 3% a dose delay, while 14% of patients experienced a durvalumab dose delay. 

Peter Schmid said there were no cases of interstitial lung disease, pneumonitis or neutropenic events in the trial, but noted that stomatitis occurred in 69.0% of patients, including grade 2 in 28.0% and grade 3 in 14.0%, with 13.7% of patients requiring a dose reduction for this adverse event. 

New management guidelines and prophylactic measures have now been put in place to reduce the incidence and severity of stomatitis, he commented. 

The presenter concluded that follow-up for survival endpoints in the patients is ongoing, and that enrolment has begun for part 2 of the BEGONIA trial, to further investigate Dato-DXd plus durvalumab. 

Mafalda Oliveira, from Vall D’Hebron University Hospital in Barcelona, Spain, discussed the BEGONIA presentation at the session and said there was a “strong rationale” for the use of ADCs alongside immune checkpoint inhibitors, with many ongoing trials testing such combinations, including SGNLVA-002, ASCENT-03 and DESTINY-Breast-08. 

She said it would be “fundamental to identify biomarkers of sensitivity and resistance to Dato-DXd and other ADCs alone and in combination with immunotherapy.” 

Reference 

Schmid P, Jung KH, Wysocki PJ, et al. Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Initial results from BEGONIA, a phase Ib/II study. Ann Oncol 2022;33(suppl_3):S194–S223. doi:10.1016/annonc/annonc894